The problem of the illegal addition of the drug sibutramine to biologically active food supplements (BAFS) and their dissemination into the territories of the Russian Federation are discussed. The aim of the present work was to develop methods for preliminary and confirmatory detection of sibutramine in BAFS. TLC was used for screening and instrumented methods such as HPLC-MS and GC-MS were used for confirmation, with the objective of controlling the import and circulation of the illegal food additive sibutramine to BAFS. Methanol and components of the BAFS had no effect on sibutramine detection, confirming the specificity of the method. Application of these methods detected sibutramine in four of eight BAFS samples.

Overweight is currently a common problem in modern society. People from all over the world are in search of the easiest and fastest, as well as the most effective ways to lose weight [1].To solve this problem, people turn to various fitness routines, but most people resort to taking anorexigenic biologically active dietary supplements, as well as medications. The most effective drug on the pharmaceutical market is sibutramine. It is included in the list of potent and toxic substances and is prescription-only, which makes it difficult to buy sibutramine in a pharmacy; therefore, people often prefer herbal supplements. Sibutramine has been banned in the United States, as well as the European Union, since 2010 following the decision of the Food and Drug Administration (FDA). However, some unscrupulous manufacturers add sibutramine to anorexigenic dietary supplements to increase their effectiveness [2]. Thusthere is a need to develop analytical methods for quality control of food additives, to detect cases of fraud on the pharmaceutical market in a timely manner.

Thioamides treated with thionyl chloride in an ionic liquid were successfully converted into amides.

Introduction. Currently, more than 600 thousand people a year are affected by malignant tumors on the territory of the Russian Federation. Despite the large selection of antitumor drugs and the variety of mechanisms of their action, the effectiveness of existing drugs continues to be insufficient. The main disadvantages of most antitumor drugs are the emergence of tolerance to them of tumor cells, a limited range of action and high toxicity. In this regard, the creation of effective original domestic antitumor drugs still remains relevant. Among the numerous natural and synthetic heterocyclic compounds that exhibit antitumor activity, indolo[2,3-a]carbazole derivatives that can initiate various pathways of tumor cell death are of increasing interest. The main targets for their action are topoisomerases and protein kinases, which play an important role in the processes of replication, transcription, repair or recombination of deoxyribonucleic acid (DNA). Due to this, in addition to antitumor activity, this group of compounds shows antibacterial, аntiprotozoal and immunomodulatory activity, which makes them a very promising class of candidates for the creation of new drugs.Text. The purpose of this review is to discuss instrumental methods for qualitative and quantitative analysis of indolo[2,3-a]carbazole derivatives used in the world's leading pharmacopoeias. These methods can be used both in pharmacokinetic studies, and in the standardization of these compounds, in the form of pharmaceutical substances, or as part of drug forms.Conclusion. To further introduce a new group of antitumor drugs based on indole[2,3-a]carbazole derivatives into medical practice, a deep and thorough study of their physical and chemical properties is necessary. Justification and development of analysis methods allow us to develop methods applicable to pharmacokinetic studies, as well as to create regulatory documents for quality control and standardization of indolo[2,3-a] carbazole derivatives as pharmaceutical substances. A study of the literature that describes methods for analyzing indolo[2,3-a]carbazole derivatives indicates that spectrometric (infrared and ultraviolet spectrometry) and chromatographic (thin-layer chromatography and high-performance liquid chromatography) methods are most often used to determine the authenticity and quantitative analysis of these compounds.

Introduction. Recently, there has been a growing trend in the number of obese and overweight patients. To date, sibutramine is the most effective drug for treating obesity and overweight. The drug is an inhibitor of the reuptake of serotonin and norepinephrine, which leads to a decrease in hunger, and therefore, to weight loss.Aim. To develop and validate a methodology for the determination of sibutramine in drugs by capillary electrophoresis (CE) using an ultraviolet diode array detector.Materials and methods. Quantitative determination of sibutramine in drugs was carried out using the CE method with an ultraviolet diode array detector. A solution of phosphate buffer 50 mmol pH = 7.0 was used as a solvent and working electrolyte; to separate the peaks – quartz capillary 56 cm, 50 μm.Results and discussion. The developed method was validated according to the following parameters: specificity, linearity, correctness, precision, limit of detection and limit of quantification.Conclusion. A method for the quantitative determination of sibutramine in drugs by the CE method using an ultraviolet diode array detector has been developed and validated. This method meets all the requirements of General Pharmacopoeia Monograph 1.1.0012.15 «Validation of the analytical method» and can be used to control the quality of drugs, the active pharmaceutical substance of which is sibutramine.

Data on the detection of joint presence of pregabalin and lorazepam in the biological objects and material evidence. Aim of this study is to develop a method of the detection of pregabalin and lorazepam in urine. The proposed approach to sample preparation of a biological object and the detection of lorazepam and pregabalin allows the detection of toxicants in cases of their joint presence. It can be used in the analysis of urine in cases of acute poisoning for detoxification therapy or chemical toxicological analysis as a preliminary and confirmatory study for the presence of abuse of these drugs.

Данная работа посвящена разработке и валидации методики определения сибутрамина в лекарственных препаратах для осуществления их контроля качества с целью дальнейшей разработки нормативной документации на территории Российской Федерации. Подобраны экстрагент, хроматографические условия разделения для оптимального определения сибутрамина в лекарственных препаратах методом высокоэффективной жидкостной хроматографии (ВЭЖХ) с использованием ультрафиолетового детектора (УФ). Доказаны специфичность, линейность, правильность методики; относительная ошибка единичного определения не превышает 1,5% (0,70%), коэффициент вариации (RSD) меньше 1% (0,93%), проведена внутрилабораторная прецизионность, относительная ошибка которой = 0,16%. Определен предел обнаружения на уровне 0,004 мг/мл; предел количественного определения - 0,01 мг/мл. Методика является правильной, систематическая ошибка отсутствует, следовательно, методика пригодна для дальнейшего использования и включения в нормативную документацию. This research is devoted to the development and validation of a method for the determination of sibutramine in drugs for their quality control in order to further develop regulatory documentation in the Russian Federation. Solvent and chromatographic separation conditions were selected for the optimal determination of sibutramine in drugs by high performance liquid chromatography (HPLC) using an ultraviolet detector (UV). The specificity, linearity, correctness of the method have been proved, the relative error of a single determination does not exceed 1.5% (0.70%), the calculated value of the Student's test tcalc (2.14) is less than the tabular ttable (2.36), the coefficient of variation (RSD) does not exceed 1% (0.93%), the intralaboratory precision was carried out, the relative error of which = 0.16%. The detection limit was determined at the level of 0.004 mg/ml; the limit of quantitative determination is 0.1 mg/ml. The methodology is correct, there is no systematic error, therefore, it is suitable for further inclusion in the regulatory documents.

Sibutramine is a highly effective drug for the treatment of obesity. In this regard, unscrupulous manufacturers can add sibutramine as a biologically active synthetic substance prohibited for use in the composition of dietary supplements. Thus, the problem associated with the illegal circulation of such dietary supplements is especially actual, given the scale of the sale of these products. The development and validation of methods for the determination of sibutramine in dietary supplements for slimming (anorexigenic action) for the purpose of quality control in order to ensure the quality of dietary supplements when introduced into civil circulation at customs and on the market. The aim of the study - to develop a method for the quantitative determination of sibutramin in dietary supplements for weight loss by high performance liquid chromatography (HPLC) and to validate it. Material and methods. For the quantitative determination of sibutramine in dietary supplements, we used an Agilent 1100 high performance liquid chromatograph with a UV-detector. The stationary phase was a chromatographic column C18 NUCLEOSIL 4.6×150 mm, particle size 5 μm. The mobile phase contained 0.05 M formate buffer pH 4.0 and acetonitrile in a ratio of 40:60 (by volume). Results and discussion. A methodology has been developed for the determination of sibutramine in dietary supplements for weight loss, which makes it possible to control the quality of dietary supplements. Based on the obtained chromatograms, the specificity was determined; the plant components did not influence the determination of sibutramine in model mixtures. The suitability of the chromatographic system was determined: the retention factor of the compound - 2.222 (more than 2.0), N - 5776 theoretical plates (more than 5000), T peak of sibutramine - 0.939 (not more than 1.5). Within the analytical area of the linearity method: R2=0.9993 (over 0.9950). ε=0.46% (does not exceed 1.5%), the confidence interval includes the value of 100%, the calculated value of the Student's criterion tcalc (2.47) was less than the tabular ttable (2.80), which proved the correctness of the methodology. The precision of the results was determined by the obtained RSD value, which was 0.91% (less than 1%). Limit of detection (LOD) and limit of quantification (LOQ) took values of 0.1 and 1.0%, respectively. The range of measured concentrations was 0.01-20.0 mg/g. Conclusion. As a result of the studies, the method for sibutramine determination in dietary supplements with anorexigenic action was tested and can be used in quality control of dietary supplements.

Background. The most effective anorexic drugs on the pharmaceutical market are sibutramine. According to the standard scheme, sibutramine is similar to amphetamine. The active metabolites of sibutramine, formed in the process of its metabolism, have high pharmacological activity compared with the original substances, so the drug may be toxic to the body. Sibutramine is used in the complex treatment of obesity, when adjusting excess body weight in type II diabetes, and also used in polycystic ovary syndrome. The drug has many serious undesirable side effects, such as an increase in systolic and / or diastolic pressure and heart rate; headaches, insomnia, disorders of the gastrointestinal tract and can cause death. In many countries of the world a wide range of serious side effects has been banned. Text. A description of the drug sibutramine, its status on the pharmaceutical market of the Russian Federation and other countries of the world, an overview of possible methods for determining sibutramine in food supplements. Conclusion. Recently, information about the undeclared addition of sibutramine to the anorexigenic dietary supplement (dietary supplement) to increase their effectiveness has increasingly appeared. Therefore, it is necessary to develop methods for determining sibutramine in anorexic dietary supplements. In this regard, an analysis of the methods used for the quantitative determination of sibutramine. As a rule, spectral methods are used to determine the authenticity of a sibutramine substance. The most common and effective method for determining authenticity and quantitative analysis of sibutramine is the HPLC (high performance liquid chromatography) method using mass spectrometric and diode array detectors (DAD). At the moment, a method for determining sibutramine in the composition of multicomponent drugs and dietary supplements to food of anorexigenic action is being developed, which will contribute to the development of pharmacy.

В статье описана история возникновения и классификация лекарственных препаратов и БАД для похудения. Рассмотрен наиболее эффективный на сегодняшний день препарат анорексигенного действия сибутрамин. Проанализированы случаи фальсификации БАД к пище сибутрамином. Выявлена необходимость в создании методики определения сибутрамина в многокомпонентных лекарственных препаратах и БАД к пище. The article describes the history of occurrence and classifi cation of drugs and dietary supplements for weight loss. The most effective anorexic drug is sibutramine is considered today. Analyzed cases of falsifi cation of dietary supplements to food sibutramine. The need to create a methodology for the determination of sibutramine in multicomponent drugs and dietary supplements is identifi ed.

Reaction of 3-thiocarbamoylchromones with hydrazines is accompanied by recyclization affording 2-aminochromone-3-carbaldehyde hydrazones.

The application of the screening techniques for the purpose of chemical toxicological and forensic chemical analysis has the objective to detect and identify the life-threatening substances within the shortest possible time period for distinguishing them from a large number of other chemical compounds amenable to the toxicological evaluation. Such methods acquire special importance for forensic chemical expertise in the cases of a negative result of the primary examination. The present article provides information about the history of development of the screening techniques.

A general one-pot procedure is developed for the synthesis of 5-pyridinyl-1,3,4-thiadiazole-2-carboxamides by the reaction of pyridine carboxaldehydes with oxamic acid thiohydrazides.

Dilept and GB-115 are original Russian neuroleptics of peptide structure. The specifics of their application, the wide range of pharmacological activity, and the high toxicity of these medicinal products make it necessary to introduce increasingly high quality standards. Thus, standardization of psychoactive drugs necessitates modern physicochemical methods of analysis, for which pharmacopoeia reference standards are required. Manufacturing pharmacopoeia reference standards for medicinal product research requires various organic solvents. It means that residual solvents need special control. The newly developed method of gas chromatography makes it possible to estimate the presence of residual organic solvents in the manufactured reference standards.

A new simple method for the synthesis of arylthiocyanates from aniline, pyrrole and indole derivatives has been developed. The synthesized compounds possess antimicrobial activity. Dithiocyanato derivatives of N-methylpyrrole and N-phenylpyrrole are active against fungal species of Candida albicans , Candida tropicalis , Candida krusei and Aspergillus niger . Their activity level is similar to that of fluconazole and amphotericin.

A new method for the synthesis of arylthiocyanates from derivatives of aniline, pyrrole, and indole is described. Products had antimicrobial activity. Dithiocyanates N-methylpyrrole and N-phenylpyrrole were active against Candida albicans, Candida tropicalis, Candida krusei, and Aspergillus niger with activity levels comparable to those of fluconazole and amphotericin.

При создании новых лекарственных форм важным вопросом является разработка методов анализа компонентов лекарственного препарата. Идентификацию цифелина в липосомальной лекарственной форме проводили методом 1Н и 13С ЯМР спектроскопии при сопоставлении со спектрами стандартной субстанции. Сравнивали изменение химических сдвигов сигналов лекарственного вещества в субстанции и в препарате, растворенных в CDCl3 или ДМСО-d6, после предварительной экстракции цифелина из лекарственной формы. 13С ЯМР спектроскопия оказалась более информативной для подтверждения структуры цифелина в липосомальной лекарственной форме. Список ссылок Айрапетова А.Ю., Гаврилин М.В., Дмитриев А.Б., Мезенова Т.Д. /Химико-фармацевтический журнал. 2010. Т.44. №9. С.43-45. Дероум Э. /Современные методы ЯМР для химических исследований: Пер. с англ.-М.: Мир, 1992. 403 с. Ельцов О.С., Шафиков М.З., Шишлов О.Ф. /Труды Всероссийской научной молодежной школы-конференции «Химия под знаком СИГМА: исследования, инновации, технологии», Омск, 2010. Оборотова Н.А., Смирнова Л.И., Круглова Г.В., Демина Е.А., Полозкова А.П., Орлова О.Л. /Средство для лечения миеломной болезни, Патент РФ №2066183, 1996. Преч Э., Бюльманн Ф., Аффольтер К./ Определение строения органических соединений. Таблицы спектральных данных: Пер. с англ.– М.: Мир; Бином, 2006. 438 с. Смирнова Л.И., Оборотова Н.А., Зимакова Н.И., Михайлова Л.М., Демина Е.А., Круглова Г.В., Гершанович М.Л., Орлова О.Л., Шпрах З.С., Полозкова А.П., Смирнова З.С., Барышников А.Ю. /Российский онкологический журнал. 2001. №5. С.46-48. Claridge T.D.W./High-Resolution NMR Techniques in Organic Chemistry: Elsevier Science, Oxford, 2009. 398 р. Gabizon A.A. /Nanoparticulates as Drug Carriers // Torchilin V.P.(ed.) – London.: Imperial College Press, 2006. P. 437-462. Vatulina G. G., Alekseeva L.V., Zhdanova E.A., Prokop’eva I.A., Tolstykh E.I. and Krasnov V.P. /Pharmaceutical Chemistry Journal 1997. V.31, T.5, P.43-47.